The proposed investigation is an examination of the effects of non-opiate drugs on three properties of morphine which are associated with its use--physical dependence, tolerance, and withdrawal. Mice and rats will be made tolerant to the effects of phenobarbital, diazepam, or amphetamine, then the various aspects of morphine action will be studied. The experiments are designed to be carried out in three separate phases. Firstly, we intend to determine the duration of opiate-receptor interaction necessary for physical dependence to be initiated and to then evaluate the degree of permanence of this initial physiological change. Secondly, the development of tolerance to the analgesic effects of morphine will be studied, employing the tail-flick test, in animals tolerant to one or another of the non-opiate drugs. Thirdly, spontaneous and drug-induced morphine withdrawal will be evaluated using hormonal and behavioral indices in animals codependent on other drugs. The use of plasma corticosterone levels to indicate the stress of withdrawal is possible through the use of enclosed experimental chambers and appropriate surgical procedures. Blood samples are obtained and injections made through a chronic indwelling catheter inserted via the external jugular vein to the entrance of the right atrium. Our expectation is that the results of this investigation will lend insight into factors underlying the problem of narcotic abuse, drug interaction, and multi-drug dependence.